Geron trial approval marks new era for stem cell research

In a breakthrough hailed as a milestone for clinical research and the harbinger of a more accommodating US environment for stem cell research under the Obama administration, Geron Corporation has secured clearance from the Food and Drug Administration (FDA) for what the company says will be the world’s first study of a human embryonic stem cell (hESC)-based therapy in humans.

The Californian biopharmaceutical specialist will initiate a small, multicentre Phase I safety trial of GRNOPC1 in patients with acute spinal cord injuries. The FDA had put Geron’s 21,000-page Investigational New Drug (IND) application for GRNOPC1 on clinical hold last May.

According to Dr Thomas Okarma, Geron’s president and chief executive officer, the agency’s decision to let the trial go ahead “marks the beginning of what is potentially a new chapter in medical therapeutics – one that reaches beyond pills to a new level of healing: the restoration of organ and tissue function achieved by the injection of healthy replacement cells”.

GRNOPC1 is Geron’s lead hESC-based therapeutic candidate and contains oligodendrocyte progenitor cells, derived from human embryonic stem cells, that have demonstrated remyelinating (the ability to regenerate a nerve’s myelin sheath) and nerve growth-stimulating properties leading to restoration of function in animal models of acute spinal cord injury, the company noted.

Geron has selected up to seven US medical centres as candidates to participate in the Phase I study and planned protocol extensions. Eligible patients must have documented evidence of functionally complete spinal cord injury with a neurological level of T3 to T10 spinal segments. GRNOPC1 will be injected into the lesion sites between seven and 14 days after injury. While the primary study endpoint will be safety, the protocol will include secondary endpoints to assess efficacy, such as improved neuromuscular control or sensation in the trunk or lower extremities.

Once safety has been established in this patient population and the FDA has reviewed the data in conjunction with additional evidence from ongoing animal studies, Geron plans to seek approval to increase the dose of GRNOPC1, enrol subjects with complete cervical injuries and extend the trial to patients with severe incomplete (American Spinal Injury Association grade B and C) injuries, “to enable access to the therapy for as broad a population of severe spinal cord-injured patients as is medically appropriate”.

Although commentators have drawn parallels with the new dawn of the Obama inauguration, and President Obama is widely expected to lift the Bush-era restrictions on federal funding for embryonic stem-cell research, in truth this relationship is largely symbolic.

An executive order passed by former President George W Bush in August 2001 severely limited federal backing for embryonic stem cell research by banning funding for projects that used anything other than the 22 or so embryonic stem cell lines then available for study.

However, as Geron explained to the press, GRNOPC1 was based on ESC lines that predated the 2001 order, and the company did not apply for federal funding anyway. Where Geron did suffer from the Bush policy was in the lack of published research to help the FDA in evaluating the company’s IND for GRNOPC1.